Phase II multicenter clinical trial: Mosunetuzumab for early relapse of follicular lymphoma in the Nordic countries (MERLIN/NLG-FL6/ML43841)

Prior treatment

• Received 2 or more previous treatment lines.
• Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects with a previous hepatitis B infection will be eligible if they are negative for HBV-DNA; these subjects must be given prophylactic antiviral therapy. Subjects with a previous HCV infection will be eligible if they are negative for HCV-RNA.
• Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to the first dose of mosunetuzumab.
• Administration of live vaccines within four weeks of the first dose of mosunetuzumab or anticipation that live vaccine will be required during the study.
• Prior allogeneic hematopoietic stem cell transplant.
• CNS involvement (current or previous)

Other illness

• Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension.
• Known or suspected chronic active Epstein-Barr virus (EBV) infection.
• History of severe allergic or anaphylactic reactions to chimeric, human, or humanized antibodies, or fusion proteins.
• Known or suspected hemophagocytic syndrome.
• Active severe infection.
• Current or previous other malignancy within three years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancy without sponsor approval.
• Psychiatric disorder or dementia which make the patient unable to give an informed consent and/or adhere to the schedule.
• Severe cardiac disease: impaired cardiac function (NYHA class III or IV), myocardial infarction within the last 6 months, unstable arrythmias and/or unstable angina pectoris.

Lab values

• Impaired liver function not caused by lymphoma, defined as serum total bilirubin ≥ 1.5 x ULN (unless elevated due to Gilbert’s syndrome) or serum ALT and AST ˃ 3 x ULN
• Impaired renal function not caused by lymphoma, defined as calculated creatinine clearance <= 40 ml/minute
• HIV positivity: Subjects that are on HIV-treatment with undetectable HIV-RNA and CD4-counts above 200 will be eligible.
• Impaired bone marrow function (neutrophils < 1.0 x 10^9/L or platelets < 50 x 10^9/L) unless due to lymphoma involvement

Other

• Grade 3b FL.
• Other major organ dysfunction not caused by lymphoma
• Women of reproductive potential not agreeing to use an acceptable method of birth control during treatment and for three months after completion of treatment.
• Other current severe medical problems or expected survival of less than approximately five years for non-lymphoma reasons.
• CD20-negative lymphoma
• Pregnancy or breast-feeding.

• Written informed consent according to ICH-GCP guidelines
• Age ≥ 18 years
• Follicular lymphoma grade 1-3a with a current relapse or progression within 24 months of starting 1st line treatment or refractory to 1st line treatment (POD24), more specifically: a. Documented current relapse or progression of FL within 24 months of starting first line treatment containing a monospecific anti-CD20 antibody (such as rituximab or obinutuzumab with or without chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide). b. Alternatively, current lack of response/refractoriness to first line treatment, i.e., no objective response or documented progression within 6 months following at least four cycles of monotherapy with a monospecific anti-CD20 antibody (such as rituximab 375mg/m2 iv or 1400 mg SC or equal) or following at least three cycles of a monospecific anti CD20 antibody combined with chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide. c. Received one prior treatment line of systemic therapy. d. If the POD24 event was diagnosed more than three months ago, then study inclusion has been clarified with the coordinating investigator. e. Patients may have received localized radiotherapy previously. Patients may have received localized radiotherapy previously. If the radiotherapy was recent, the patient must have at least one progressive and measurable lesion outside the radiation field.
• At least one two-dimensionally measurable lesion with a longest diameter >15mm.
• WHO performance status 0-2. Patients with reduced WHO performance status (> 2) can be considered if reduction in performance is caused by the lymphoma as determined by the investigator.